Viscoelastic Properties of Rodent Mammary Tumors Using Ultrasonic Shear-Wave Imaging

Abstract

Images of tumor mechanical properties provide important insights into malignant-cell processes manifest by extracellular matrix (ECM) stiffening and remodeling. This article presents a pilot study measuring in vivo mechanical-property characteristics of rodent mammary tumors using an ultrasonic shear-wave imaging technique. Shear waves are generated by a needle inserted into the tumor of anesthetized rodents that is vibrated harmonically between 50 and 450 Hz. Particle motion in the tumor associated with the radiation of cylindrical shear waves is imaged using pulsed-Doppler ultrasound techniques. Estimating the spatial gradient of shear-wave phase along the direction of propagation at frequencies in the measurement range yields shear-speed dispersion curves. Measured dispersion curves were fit to those predicted by three different rheological models to estimate the elastic and viscous coefficients of the complex shear modulus. The investigation was performed in vivo on four rat-mammary fibroadenoma tumors and five xenograft mouse-mammary carcinoma tumors. Each tumor was subsequently excised for histological imaging and composition analysis. Collagen composition was measured using hydroxyproline assays that were then correlated with mechanical measurements. The goal was to relate soft-tissue mechanical behavior to biological characteristics of tumor structures, specifically the collagenous ECM protein content. The choice of rheological model and the effects of artifacts induced by shear-wave reflections at internal tissue boundaries are carefully examined in this article. Addressing these issues is of great importance when selecting force-excitation methods and modulus estimation method to assess intrinsic tissue properties responsible for disease-specific elastographic contrast.